A condition generally called Xerostomia or dry mouth is characterized by diminished or deficient salivary secretion induced by various causes, and commonly occurs. Since so many factors are involved in salivary secretion, it is remarkably difficult to find out causes of xerostomia. Examples of known causes of this condition include various diseases causing organic change of salivary glands; pathological changes of salivary glands caused by systemic diseases; damaged salivary glands owing to radiotherapy; HIV infection (AIDS); secretory hypofunction owing to aging; and effects of administration of various drugs. In addition, this condition is known to be brought on by mental fatigue or stress under complicated environment in social life.
Symptoms of xerostomia are usual, especially among elderly people. Approximately 16% of males and 25% of females in a group of elderly people aged 70 or older have symptoms of xerostomia. This may be because of regressive change of salivary glands owing to aging, and decreased salivary secretion associated with this change. Effects of various drugs are also pointed out as causes of xerostomia. Examples of drugs that may cause xerostomia include: diuretics such as trichloromethiazide and furosemide, hypotensors such as reserpine and clonidine hydrochloride, anticholinergic agents such as atropine sulfate, and antihistamines such as chlorophenylamine maleate. Other examples thereof include various expectorant/cough suppressants, anti-Parkinson drugs, psychotropic drugs, antidepressants, tranquilizers and muscle relaxants. Radiotherapy has become increasingly important for treating malignant tumors in oral surgery and otolaryngology fields, and almost inevitably causes severe damage to salivary glands by radioactive rays owing to the irradiation area. This damage often results in especially severe xerostomia. The number of patients suffering from xerostomia is expected to increase with widespread use of the radiotherapy.
Patients with xerostomia have a dry feeling in the mouth, and also may experience symptoms such as a burning feeling in the mouth, oral pain, glossodynia, dysgeusia, atrophy of lingual-papillae, oral mucosal inflammation, mouth sores, ulcers, cracked tongues, cracked mouth corner, other difficulties in mastication, swallowing, phonation and speech, interrupted sleep and eating disorder. Some patients have to take nourishment into their bodies by way of tube feeding or intravenous drip. Xerostomia causes dental disorders including oral mucous membrane ulcers, dental caries and periodontosis, oral infections and respiratory tract infections at an increased frequency, and also causes bad breath. There is a strong demand for appropriate solutions to these problems.
As a product for relieving xerostomia, artificial saliva, gargles, moisturizing mouthwashes containing hyaluronic acid and chondroitin sulfate, and the like are currently used, and can only temporarily hydrate the mouth. Salivary secretion accelerators (e.g. cevimeline hydrochloride) or various Kampo medicines also have been used for the purpose of relieving xerostomia. However, the use thereof causes unfavorable side effects in some cases, and does not deliver sufficient effects for relieving or preventing xerostomia.
Coenzyme Q is known to be subcategorized into coenzyme Q1 to coenzyme Q13 according to the repetitive structure of the side chain. Coenzyme Q10 is the predominantly occurring form of coenzyme Q in many mammals, and therefore coenzyme Q10 occurs in humans. Coenzyme Q is topically present in mitochondria, lysosomes, Golgi bodies, microsomes, peroxisomes, cell membranes or the like, and it is essential for maintaining functions in living bodies because coenzyme Q is known to be involved in activation of ATP production as a component of the electron transfer system in mitochondria, and antioxidant action and stabilization of membranes in vivo. Coenzyme Q is known to transfer electrons by repeating oxidation and reduction in the electron transfer system.
It is known that coenzyme Q can be in an oxidized form and a reduced form. The oxidized coenzyme is named “ubiquinone”, and the reduced coenzyme is named “ubiquinol”. Coenzyme Q in vivo is mostly in the reduced form since coenzyme Q in the oxidized form is absorbed in the body to be intracellularly converted into the reduced form by a reductase. Reduced coenzyme Q provides antioxidant action when reacting with active oxygen in the body. Namely, reduced coenzyme Q exhibits antioxidant activity. Reduced coenzyme Q is regarded as a main active ingredient in vivo based on the above-mentioned facts that coenzyme Q is mostly in the reduced form in vivo and only the reduced coenzyme Q exhibits antioxidant activity.
Reduced coenzyme Q is, however, easily oxidized in air and thereby converted into oxidized coenzyme Q. Therefore, the stability of reduced coenzyme Q in air is problematic. For this reason, only oxidized coenzyme Q has been industrially utilized owing to its favorable stability in air. Based on this background, the term “coenzyme Q” in previous documents generally indicates oxidized coenzyme Q, unless otherwise specified. The reduced coenzyme is described as “ubiquinol” or “reduced coenzyme Q” instead of being simply described as “coenzyme Q”.
Oxidized coenzyme Q has been conventionally used as an adjuvant for congestive heart failure. In recent years, oxidized coenzyme Q is widely used in health foods all over the world. Oxidized coenzyme Q has been widely studied on its physiological activities and is known to have various physiological activities such as anti-diabetes, anti-fatigue and anti-arteriosclerosis activities (See Patent Documents 1 to 3). There have been very few reports on side effects of this compound. A safety test in animals in which this compound was administered to rats for 52 consecutive weeks at a high dose of 1.2 g/kg/day resulted in no evidence of toxicity, and thereby proved high safety of this compound (See Non-Patent Document 1).
Oxidized coenzyme Q was reported to exhibit effects to improve conditions of Parkinson's disease model mice, one of typical neurodegenerative diseases (See Non-Patent Document 2). There have been reports on similar suppression effects of oxidized coenzyme Q used in in vitro systems of nerve cells in which cell death is induced by exposure to hydrogen peroxide (See Non-Patent Documents 3 and 4).
However, no reports on efficacy of coenzyme Q in xerostomia have been made.
Patent Document 1: JP-A H07-330584
Patent Document 2: JP-A H07-330593
Patent Document 3: JP-A H07-287560
Non-Patent Document 1: J. Agric. Food Chem., 1999, Vol. 47, 3756-3763
Non-Patent Document 2: Free Radical Research, 2002, Vol. 36, 455-460
Non-Patent Document 3: Archives of Biochemistry and Biophysics, 2004, Vol. 421, 54-60
Non-Patent Document 4: Neurobiology of Disease, 2005, Vol. 18, 618-627